Genotoxicity blocking

CYP [antimutagenic, anti-genotoxic, block xenobiotic conversion to genotoxics] CYP - CYP3A4 (17)... 

It has been suggested that phenol exposure results in cardiac effects because it blocks the cardiac sodium channel subtype, with little effect on sodium channels in skeletal muscle (Zamponi et al. 1994). Phenol does not appear to be carcinogenic following oral exposure (NCI 1980), although the chemical combinations that result from benzene and phenol metabolism may contain compounds that do initiate or promote cancer. Metabolites such as hydroquinone and catechol have been demonstrated to be genotoxic and clastogenic. 

Moreover, overexpression of the same mutants inhibit DNA replication and block the cells at the Gl/S-phase transition (Kim et al, 2005), emphasizing the potential role of nucleolin mobilization. It is therefore highly probable that two different processes help the formation of RPA-nucleolin complexes after a genotoxic stress a post-transcriptional modification of nucleolin that renders the GAR domain of nucleolin accessible to RPA, and its p53-dependent relocalization to the nucleoplasm where a higher amount of RPA is available. Of importance, nucleolin relocalization is transient and lasts far less than replication inhibition (Daniely and Borowiec, 2000). This means that nucleolin-RPA interaction is only an initial event and that other mechanisms account for prolonged replication inhibition. 

Anethole is known to block the nuclear factor kappa B activation process [359] that is linked with cancer proliferation [272,360]. trans-Anethole was also found to inhibit the in vivo genotoxicity of xenobionts [345]. 

Seoane AI and Dulout FN (2001) Genotoxic ability of cadmium, chromium and nickel salts studied by kinetochore staining in the cytokinesis-blocked micronucleus assay. Mutat Res 490 99-106. 

Because antiestrogens are able to block the estrogen-indnced carcinogenesis, it is reasonable to believe that these genotoxic and epigenetic events may be mediated throngh estrogen receptors. Further studies are warranted to reconcile this issne. 

No genotoxic activity of the compounds (+)-usnic acid and (-)-usnic acid was observed in the cytokinesis-blocked... 

In vitro studies have been described by Watson et al., who aimed to mimic the chemical reactions that could deplete vitamin B12 as a result of human exposure to electrophilic xenobiotics (styrene, chloroprene and 1,3-butadiene) [258]. It was shown that NADPH in liver microsomes converts hydroxycobalamin not only to cob(II)alamin (23) but also to cob(I)alamin (40"), both of which react with the genotoxic epoxides of chloroprene and 1,3-butadiene to form their respective organometallic derivatives. With styrene, the metabolically formed styrene oxide reacted with 40" alone. The findings also showed though, that when glutathione was added, these reactions are blocked due to the formation of glutathionylcobalamin and it was postulated that this acts as a protective reservoir for vitamin B12 (1) by inhibiting alkylation by epoxides and alkyl halides [258]. 

Fig. 6.2 Photomicrographs for some genotoxicity assays, (a) A mitogen-stimulated cytokinesis-block lymphocyte containing one MN Giemsa staining of BrdU-incorporated chromosomes in human lymphocytes for SCE (b), arrowheads show chromosome breaks and sister union and for CA (c) sister chromatids stained at different density (photograph kindly provided by Dr. B. Ayaz Tuylu). (d) COMET tails of chromosomes visualised by an epifluorescence microscope (photograph kindly provided by Dr. A. T. Koparal)...

Einarsdottir E, Groeneweg J, Bjomsdottir GG et al (2010) Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med 76 969-974 Fenech M (2007) Cytokinesis-block micronucleus cytrane assay. Nat Protoc 2 1084-1104 Geyikoglu F, Tiirkez H, Aslan A (2007) The protective roles of some lichen species on colloidal bismuth subcitrate genotoxicity. Toxicol Ind Health 23(8) 487-492... 

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